Oral care product

ABSTRACT

An oral care product comprising a first composition comprising an insoluble calcium salt that is not a calcium phosphate salt, a second independent composition comprising a source of phosphate ions, and a means for delivering each of the compositions to the surface of the teeth.

The present invention relates to an oral care product suitable for maintaining and/or enhancing the quality of teeth. The product comprises compositions that react together to ultimately form hydroxyapatite on the teeth surface, a material that can lead to remineralisation and/or whitening of the teeth.

Due to today's lifestyles with increasing consumption of acidic drinks and foods, tooth erosion is becoming more prevalent and common. Enamel, the hard, protective coating of the tooth, is susceptible to attack by acid, leading to the enamel becoming softer and ultimately to the exposure of the sensitive dentin underneath the enamel. There is a need to reduce or counter the erosion of peoples' tooth enamel in order to maintain good oral health.

Many oral care products seek to counter erosion of enamel by “remineralisation” using fluoride ions according to the following reaction scheme:

Ca₅(PO₄)₃OH →Ca₅(PO₄)₃F

The hydroxyl ion is replaced by the fluoride ion and the resulting fluoroapatite composition is harder than the original hydroxyapatite composition and more resistant to the acidic attack. Unfortunately, however, such ion replacement through fluoride treatment cannot achieve a complete restoration of the lost minerals. The method is a preventive treatment and does not actively recover demineralised teeth to their original chemical and mechanical state.

The enamel layer of the tooth is naturally an opaque white or slightly off-white colour; however, this enamel layer can become stained or discoloured. The enamel layer of the tooth is composed of hydroxyapatite mineral crystals that create a somewhat porous surface. It is believed that this porous nature of the enamel layer is what allows staining agents and discolouring substances to permeate the enamel and discolour the tooth.

Many substances can stain or reduce the whiteness of one's teeth; in particular, certain foods, tobacco products, and fluids such as tea and coffee. These staining and discolouring substances are often able to permeate the enamel layer. This problem occurs gradually over many years, but imparts a noticeable discoloration of the enamel of one's teeth.

A variety of products are currently used for teeth whitening. Such products often comprise a peroxide compound (alone or on combination with enzymes). Such products may be used in the form of strips. Such products generally have to be removed after a well defined time, the peroxide causing damage to the teeth and/or gums if left too long. A particular problem with peroxide (and toothpastes comprising abrasive cleaners) is that it can roughen the surface of the teeth.

U.S. Pat. No. 5,605,675 (Enamelon, 1997) discloses a process for remineralisation of dental enamel by application of a two-phase composition; one phase containing a water-soluble calcium compound and one phase containing a water soluble inorganic phosphate and a water-soluble fluorine compound.

U.S. Pat. No. 4,083,955 (P&G, 1978) discloses a process for remineralisation of dental enamel by sequential application of two compositions, the first comprising calcium ions and second comprising phosphate ions, or vice versa.

WO 04/017929 (Septodont ou Specialites Sepodont S.A., 2004) discloses a preparation containing: an aqueous liquid part, a solid part comprising at least one silicate selected from tricalcium silicate and dicalcium silicate; calcium chloride and a water reducing agent, to be used to restore a mineralised substance, particularly in the dental field.

An object of the present invention is to provide a product which remineralises eroded teeth and/or whitens the teeth without the need for bleaching chemicals.

The present invention involves delivering an insoluble calcium salt to the surface of the teeth and converting this salt into hydroxyapatite in situ by the simultaneous or sequential application of a source of phosphate ions. The insoluble calcium salt and the phosphates ions are delivered from independent compositions and their ability to interact prematurely is thereby minimised.

The in situ generation of hydroxyapatite results in remineralisation of the teeth, potentially reducing the likelihood of tooth decay and improving the appearance of the teeth, in particular their whiteness. The teeth may also appear smoother and shinier as a result. Since many “whitening” treatments result in a roughening of the tooth surface, the ability to whiten and yet reduce surface roughness is a particular benefit of the present invention.

The in situ generation of hydroxyapatite is principally targeting at the enamel; however, it is also expected that any exposed dentin may also be beneficially affected in similar manner.

In a first aspect of the present invention, there is provided an oral care product comprising a first composition comprising an insoluble calcium salt that is not a calcium phosphate salt, a second independent composition comprising a source of phosphate ions, and a means for delivering each of the compositions to the surface of the teeth.

In a second aspect of the present invention, there is provided a method of remineralising and/or whitening the teeth comprising the steps of treating the teeth with a first composition comprising an insoluble calcium salt that is not a calcium phosphate salt and a second independent composition comprising a source of phosphate ions.

In a third aspect of the present invention, there is provided a product comprising a first composition comprising an insoluble calcium salt that is not a calcium phosphate salt in combination with a second independent composition comprising a source of phosphate ions for use as a medicament.

In a fourth aspect of the present invention, there is provided the use of a first composition comprising an insoluble calcium salt that is not a calcium phosphate salt in combination with a second independent composition comprising a source of phosphate ions for the manufacture of an oral care product. Such products may be used to improve tooth whiteness, reduce tooth decay, and/or reduce sensitivity.

It is believed that the use of an insoluble source of calcium ions enables the calcium to be deposited onto the teeth before premature interaction with phosphate in the saliva of the oral cavity can occur. Having deposited on the tooth enamel and/or dentin, slow reaction with the phosphate present in the saliva and, importantly, that added with the second composition, results in hydroxyapatite being produced exactly where it is required.

The insoluble calcium salt used in the first composition may be any salt capable of delivery to the surface of the teeth when the composition is applied, other than a calcium phosphate. Hence, calcium salts such as hydroxyapatite and fluoroapatite are not included as suitable salts.

Preferably, the insoluble calcium salt is calcium silicate, present as the composite material calcium oxide-silica: CaO—SiO₂. The use of this insoluble calcium salt is preferred because of its excellent conversion to hydroxyapatite on the tooth surface. Without wishing to be bound by theory, it is believed that the calcium silicate reacts with phosphate ions to form a calcium silicate-phosphate cement (CSPC) and that this material bonds strongly to the teeth and then gradually transforms into hydroxyapatite on the tooth surface. It is believed that the high affinity of the CSPC for the tooth surface underlies the superior remineralisation and whitening benefits obtained.

When calcium silicate is employed, its ratio of calcium to silicon (Ca:Si) may be from 1:10 to 3:1. The Ca:Si ratio is preferably from 1:5 to 2:1, more preferably from 1:3 to 1:1, and most preferably it is about 1:2. The calcium silicate may comprise mono-calcium silicate, bi-calcium silicate, or tri-calcium silicate. Higher ratios of calcium to silicate are preferred because such ratios are believed to enhance active bonding to the tooth surface and subsequent transformation into hydroxyapatite; however, lower ratios are preferred for ease of obtaining the desired pH (vide infra).

Throughout this specification, ratios of calcium to silicon (Ca:Si) should be understood to be atom ratios.

Preferably, the insoluble calcium salt is a “biomaterial”, by which is meant a material that is capable of bonding to human and/or animal tissue. It is especially preferred that the biomaterial is able to bond to tooth enamel and/or tooth dentin.

It should be understood that the terms “insoluble” and “soluble” as used in this specification refer to a material's insolubility or solubility in water at temperatures typically found in the oral cavity. Insoluble calcium salts have a solubility of less than 0.01 mol/L.

The content of the insoluble calcium salt in the first composition is typically from 0.1 to 50%, particularly from 1 to 30%, and especially from 5 to 20% by weight.

The insoluble calcium salt may be in a crystalline or amorphous state; preferably it is in an amorphous state; more preferably it is in a mesoporous state, i.e. it is a material having pores with diameters from 1 to 50 microns. Mesoporous calcium silicate is particularly preferred and is abbreviated as MCS in this specification.

In one aspect of the invention, there is present MCS having an average pore size (diameter) of preferably from 0.4 to 4 nm, more preferably from 0.4 to 3.5 nm, and most preferably from 0.4 to 3 nm.

In another aspect of the invention, there is present MCS having an average pore size (diameter) of preferably from 2 to 4 nm, more preferably from 2 to 3.5 nm, and most preferably from 2 to 3 nm.

In a further aspect of the invention, there is present MCS having an average pore size (diameter) of preferably from 1 to 2.7 nm and more preferably from 1.35 to 2.45 nm.

The pore size may be measured using any suitable method or means. For example, the pore size may be measured using BET nitrogen sorption or mercury porosimetry techniques (particularly BET nitrogen sorption techniques).

Preferably, the first composition is substantially free of phosphate ions. By the term “substantially free” we mean that relative to the weight of the calcium ions, the amount of phosphate ions is less than 2.5%, particularly less than 1%, more particularly less than 0.1%, and especially less than 0.01% by weight. It is possible to prepare calcium oxide-silica containing less than 0.005% by weight of phosphate ions by using high purity starting materials, for example using calcium nitride supplied by China National Pharmaceutical Group Corporation (SINOPHARM), Beijing, which has a purity of greater than 99%.

Preferably, the first composition is substantially free of fluoride ions. By the term “substantially free” we mean that relative to the weight of the calcium in the insoluble calcium salt, the amount of fluoride ions is less than 2.5%, particularly less than 1%, more particularly less than 0.1%, and especially less than 0.01% by weight. In the first composition as a whole, the content of fluoride ions is preferably less than 0.1%, more preferably less than 0.01%, and most preferably less than 0.001% by weight.

Calcium silicate suitable for use in the present invention may be prepared by the methods described in our co-pending application PCT/EP2007/057556.

The pH of the first composition is preferably from 7 to 11, more preferably from 8 to 10.5, and most preferably from 9 to 10.

A preferred additional component in the first composition is an acidic buffering, such as citric acid. Such agents enable the composition to be formulated at the desired pH and are particularly desirably at higher Ca:Si ratios, for example 1:1 and greater and especially 2:1 and greater.

For the avoidance of doubt, the second composition is added to the oral cavity together with the first composition. Whilst the saliva naturally present in the oral cavity provides a source of phosphate ions, this saliva should not be considered a second composition in accordance with the present invention. By adding the second composition together with the first composition, whether simultaneously or sequentially, superior remineralisation and/or whitening results.

The source of phosphate ions used in the first composition may be any source capable of delivering phosphate ions when the composition is applied to the teeth. Preferably, the source will be a water-soluble salt. Suitable water soluble salts include tri-sodium phosphate, di-sodium hydrogenphosphate, and sodium dihydrogenphosphate.

A preferred additional component in the second composition is a source of fluoride ions. The source may be, for example, sodium fluoride, stannous fluoride, or sodium monofluorophosphate. The level of fluoride ions present in the second composition is typically, from 10 mM to 100 mM, preferably from 25 mM to 75 mM, and more preferably from 40 mM to 60 mM. The fluoride ions, particularly at the preferred concentrations, can aid the reaction between the insoluble calcium salt and the phosphate ions added from the second composition and present in the saliva.

The means for delivering each of the compositions to the surface of the teeth may be any means that allows both the insoluble calcium salt in the first composition and the phosphate in the second composition to be delivered to the teeth. The delivery of the compositions may be sequential or simultaneous. In certain embodiments, for example dual phase toothpastes, the compositions are preferably delivered simultaneously.

The means of delivery may involve a dual tube having a first compartment for the first composition and a second, independent compartment for the second composition. Such a dual tube typically has one of the compartments surrounding the other. Typically, the dual tube allows for co-extrusion of the two compositions.

The means of delivery may involve a single tube having the first composition and second composition present as independent compositions within the same tube. In such embodiments, the compositions or phases are extruded from the tube as one, such extrusion being termed “contact extrusion”. In such embodiments, one the compositions may be present as stripes within the other composition. In preferred embodiments, one of the compositions is present as a sheath, surrounding the other composition in the core. In particularly preferred embodiments, the first composition is present as a core composition and the second composition surrounds this as a sheath composition.

When the first composition and second composition are present as independent compositions within the same tube, the quantity of water within each of the compositions is preferably less than 35%, more preferably less than 30%, and most preferably less than 25% by weight. In an especially preferred embodiment of this type, the first composition has less than 20% by weight of water and the second composition has less than 25% by weight of water. It has been found that minimising the quantities of water reduces premature interaction of the calcium salt and source of phosphate ions.

The compositions may be applied to the teeth as a dual-phase toothpaste, such application involving mixing of the compositions (phases) and typically involving application using a toothbrush.

One or preferably both of the compositions may be applied to the teeth as a gel composition, the treatment involving mixing of the compositions on application and typically involving the mixed compositions being left on the teeth following application. Following such application, the mixed compositions are typically left on the teeth for from 10 minutes to 10 hours and more typically from 30 minutes to 8 hours. The application may be carried daily. The compositions may be applied from independently compartments of a dual compartment tube or from independent phases of a product contained within a single container which is typically a tube.

In certain embodiments, in particular those involving a gel composition, the means of delivery may involve a tape, in particular an adhesive tape, onto which one or preferably both of the compositions are applied, prior to the strip being placed in contact with the teeth. Using this means of delivery, the compositions can be held in close contact with tooth surface, facilitating a high concentration of calcium salt and/or source of phosphate ions close to the tooth surface. Much less of the composition(s) is/are lost into the saliva using this delivery means.

Gel compositions involve the use of a gel. In a preferred embodiment, the first composition comprises a gel. The gel typically comprises a polymeric matrix, and is more typically a hydrogel (vide infra). Excluding any water present, the polymeric matrix is typically present at from 1 to 25% by weight of the composition(s) of which it is a part.

In the context of this invention, a “gel” is a colloidal system in which a porous network of interconnected nano-particles spans the volume of a liquid medium. In general, gels are apparently solid, jelly-like materials. Both by weight and volume, gels are mostly liquid in composition and thus exhibit densities similar to liquids; however, they have the structural coherence of a solid.

The polymeric matrix material may be a hydrogel which, in the context of this invention, is an insoluble polymeric network containing an absorbed aqueous phase. Typically, the polymeric network is crosslinked. Typically, the content of other liquid components in the composition(s) comprising the hydrogel is not more than 10% by weight. Typically the content of water in the composition(s) comprising a hydrogel is from 80 to 99%.

Monomers used to prepare hydrogels may be selected from vinyl alcohol and acrylate, in particular sodium acrylate. Other monomers comprising an abundance of hydrophilic groups may also be used.

Preferred hydrogels comprise a polysaccharide, polyacrylamide, or polyacrylic acid.

Suitable polysaccharides may be storage polysaccharides, such as starch or glycogen, or structural polysaccharides, such as cellulose or chitin.

Suitable polysaccharides may include saccharide units selected from one or more of the following: isomaltose, glucose, fructose, galactose, xylose, mannose, sorbose, arabinose, rhamnose, fucose, maltose, sucrose, lactose, maltulose, ribose, lyxose, allose, altrose, gulose, idose, talose, trehalose, nigerose, kojibiose, and lactulose.

Preferred hydrogels comprise one or more polysaccharides selected from the group consisting of: tamarind gum, guar gum, locust bean gum, Tara, Fenugreek, Aloe, Chia, Flaxseed, Psyllium seed, quince seed, xanthan, gellan, welan, rhamsan, dextran, curdlan, pullulan, scleroglucan, schizophyllan, chitin, hydroxyalkyl cellulose, arabinan, de-branched arabinan, arabinoxylan, galactan, pectic galactan, galactomannan, glucomannan, lichenan, mannan, pachyman, rhamnogalacturonan, acacia gum, agar, alginates, carrageenan, chitosan, clavan, hyaluronic acid, heparin, inulin, cellodextrins, cellulose, and cellulose derivatives.

Particularly preferred hydrogels comprise polysaccharides selected from the group consisting of: sodium alginate, hydroxypropyl alginate, gum carrageenan, gum grabic, guar gum, karaya gum, chitosan, pectin, and starch.

Other preferred hydrogel forming components are the Carbopol polymer, which are commercially available from Noveon.

One or both of the compositions used in accordance with the invention may also comprise further ingredients which are common in the art, such as:

-   -   antimicrobial agents, e.g. Triclosan, chlorhexidine, copper-,         zinc- and stannous salts such as zinc citrate, zinc sulphate,         zinc glycinate, sodium zinc citrate and stannous pyrophosphate,         sanguinarine extract, metronidazole, quaternary ammonium         compounds, such as cetylpyridinium chloride; bis-guanides, such         as chlorhexidine digluconate, hexetidine, octenidine, alexidine;         and halogenated bisphenolic compounds, such as 2,2′         methylenebis-(4-chloro-6-bromophenol);     -   anti-inflammatory agents such as ibuprofen, flurbiprofen,         aspirin, indomethacin etc.;     -   anti-caries agents such as sodium trimeta phosphate and casein     -   plaque buffers such as urea, calcium lactate, calcium         glycerophosphate and strontium polyacrylates;     -   vitamins such as Vitamins A, C and E;     -   plant extracts;     -   desensitising agents, e.g. potassium citrate, potassium         chloride, potassium tartrate, potassium bicarbonate, potassium         oxalate, potassium nitrate and strontium salts;     -   anti-calculus agents, e.g. alkali-metal pyrophosphates,         hypophosphite-containing polymers, organic phosphonates and         phosphocitrates etc.;     -   biomolecules, e.g. bacteriocins, antibodies, enzymes, etc.;     -   flavours, e.g. peppermint and spearmint oils;     -   proteinaceous materials such as collagen;     -   preservatives;     -   opacifying agents;     -   colouring agents;     -   pH-adjusting agents;     -   sweetening agents;     -   pharmaceutically acceptable carriers, e.g. starch, sucrose,         water or water/alcohol systems etc.;     -   surfactants, such as anionic, nonionic, cationic and         zwitterionic or amphoteric surfactants;     -   particulate abrasive materials such as silicas, aluminas,         calcium carbonates, dicalciumphosphates, calcium pyrophosphates,         hydroxyapatites, trimetaphosphates, insoluble hexametaphosphates         and so on, including agglomerated particulate abrasive         materials, usually in amounts between 3 and 60% by weight of the         oral care composition.     -   humectants such as glycerol, sorbitol, propyleneglycol, xylitol,         lactitol etc.;     -   binders and thickeners such as sodium carboxymethyl-cellulose,         xanthan gum, gum arabic etc. as well as synthetic polymers such         as polyacrylates and carboxyvinyl polymers such as Carbopol®;     -   polymeric compounds which can enhance the delivery of active         ingredients such as antimicrobial agents can also be included.         Examples of such polymers are copolymers of polyvinylmethylether         with maleic anhydride and other similar delivery enhancing         polymers, e.g. those described in DE-A-3,942,643 (Colgate);     -   buffers and salts to buffer the pH and ionic strength of the         oral care composition; and     -   other optional ingredients that may be included are e.g.         bleaching agents such as peroxy compounds e.g. potassium         peroxydiphosphate, effervescing systems such as sodium         bicarbonate/citric acid systems, colour change systems, and so         on.

SUMMARY OF THE FIGURES

FIG. 1 Scanning electronic microscopy (SEM) image of human tooth enamel surface morphology of (a) before treatment and (b) after treatment for two weeks with MCS-gel in phosphate-containing saliva in an 8 hours/day cycling treatment.

FIG. 2 SEM image of cross section view of treated tooth. A thin layer in 5 micron thickness has been formed (right bright area) on the original tooth enamel (left area).

FIG. 3 Energy Dispersive X-ray (EDX) elemental analysis of Ca and P scanned (left to right) across the dark line indicated on the SEM cross-sectional image of FIG. 2. The “distances” indicated are distances in microns.

FIG. 4 Raman spectrum of tooth surface before and after MCS-gel treatment in the presence of a phosphate containing composition.

FIG. 5 a SEM image of a tooth surface prior to “etching” with phosphoric acid.

FIG. 5 b SEM image of a tooth surface after etching with phosphoric acid.

FIG. 6 a Raman spectrum of phosphoric acid etched tooth surface.

FIG. 6 b Raman spectrum of phosphoric acid etched tooth surface following treatment with MCS-gel composition and phosphate containing composition for one week.

The following examples serve to illustrate the invention without limiting the invention to them. If not otherwise stated the percentages and parts are by weight. Examples according to the invention are designated by numbers and Comparative Examples are designated by letters.

EXAMPLES Step I Preparation of Gel Compositions Comprising MCS

Homogeneous suspensions of fine powder MCS (Ca:Si=1:2) in distilled water were formed in a range of concentrations from approximately 0.5% to 5%, as indicated in Table 1, using ultra-sonification. Sodium alginate gel particles were then added with vigorous stirring. After about 5 to 15 minutes, uniform white gel suspensions resulted. The pH of the gel suspensions were measured and are also indicated in Table 1.

TABLE 1 “First” Compositions 1 2 3 4 MSC powder 0.5 1.5 3 5 (g) Water (g) 100 100 100 100 Sodium 5 5 5 5 alginate (g) pH 9.32 9.72 9.76 10.03

Further compositions were prepared as described above with the sodium alginate present at 1 g, 1.5 g, and 3 g. The viscosity of the resulting composition was found to be a function of the alginate level, being higher at the higher alginate levels.

Step II Application of the Gel Compositions Comprising MCS

Extracted human teeth were cleaned using 75% alcohol and brushed using toothpaste to remove surface bacteria and debris. The composition designated 4 in Table 1 was uniformly painted onto the teeth at a level of 1.0 g per six teeth. The teeth were then immersed in human saliva at 37° C. After eight hours, the gel was washed off with tap water and the teeth re-immersed again in the saliva at 37° C. for the rest of day. This treatment was continued for two weeks.

The human saliva used was collected from many subjects. Its calcium concentration varied from 23 to 60 ppm and its phosphorus concentration (present as phosphate ions) varied from 124 to 154 ppm.

The surface morphology of the teeth was investigated using SEM before and after treatment. FIG. 1( a) represents the appearance before treatment and FIG. 1( b) represents the appearance after treatment. It can be seen that before treatment the surface is smooth and after treatment certain new crystalline structures have grown out from the original smooth surface. At a magnification of 10,000, tiny crystalline structures can be clearly seen, measuring about 100 nm.

To quantify the amount of newly formed hydroxyapatite, the before and after treatment tooth samples were sectioned and polished before being examined by SEM. The result is shown in FIG. 2. It can be clearly seen that a thin coating layer has been formed on the top of original enamel. The thickness of the layer varies from 2 to 10 microns, but seems to have a positive relation with the tooth surface roughness. Thus, it would appear that the treatment targets those teeth in most need of repair.

The chemical nature of the new crystalline material produced by the treatment was investigated by EDX elemental analysis (see FIG. 3) and Raman spectroscopy (see FIG. 4). FIG. 3 shows that the content of calcium and phosphorus in the newly formed hydroxyapatite is very similar to that in the original tooth enamel underneath. FIG. 4 indicates that the chemical nature of the phosphate present in newly formed hydroxyapatite is essentially the same as that of the untreated teeth, strongly suggesting that only “natural” hydroxyapatite has been added to the teeth.

Hardness Testing Using Nano-Indentation

In this experiment, the mechanical properties of the regenerated enamel layer were investigated. Mechanical robustness is of crucial importance to the long term stability of the enamel and is essential for maintenance of teeth during biting and eating food. It is desired that the enamel has a high level of mechanical hardness.

Using the same procedures as described in “Step II” (vide supra), human tooth samples were first cleaned and then treated with Composition 5 and phosphate-containing saliva on a daily basis for two weeks. On this occasion, however, an additional step was introduced: following the eight hour immersion of painted teeth in saliva, the teeth were brushed for one minute with a chalk-containing toothpaste. They were then re-immersed in saliva as in the “Step II” procedure described above.

State of the art nano-indentation instrumentation was used to measure the hardness of the thin film of newly deposited film of hydroxyapatite on the surface of the teeth. Three treated tooth samples were measured and on each sample, nine indentations were made. As shown in Table 3, the hardness of the remineralised layer is in the range of 5.4 and 5.7 GPa. This is very close to the hardness of the original enamel surface, also shown in Table 3. Another important mechanical parameter is Young's modulus, a basic value for a material's elasticity. The higher the value, the stiffer the material is. It is desirable that the remineralisation layer is similar to the natural enamel. From the results indicated in Table 3, it is clear that the remineralised film has similar mechanical properties that that of the original enamel.

TABLE 3 mechanical properties of teeth before and after treatment Young's Hardness (GPa) modulus (GPa) Before treatment 5.0-6.0  95-120 Literature values) After forming new 5.4-5.7 111-121 enamel layer

Regeneration of Damaged Teeth

To mimic the demineralization of teeth by many types of acidic fruit juice, human teeth were etched using 37 wt % phosphoric acid for one minute. Images of the original teeth and the phosphoric acid etched teeth were taken by SEM. FIG. 5 a represents a tooth surface before etching and FIG. 5 b represents a tooth surface after etching. By treatment with Composition 5 (described below) and phosphate containing saliva in the manner described above, it was found possible to cure the etching caused by the phosphoric acid within one week.

Composition 5: MCS powder (0.5 g) added to water (10 g) and dispersed as described above, then sodium alginate (0.3 g) added with vigorous stirring. A uniform gel was formed after about ten minutes stirring.

The treated samples were found to have grown a significant thickness of a new layer. The newly formed layer was characterized by Raman spectroscopy. FIG. 6 a is the Raman spectrum of a tooth surface before treatment and FIG. 6 b is the Raman spectrum of a tooth surface after treatment. Table 2 indicates the position of the major peaks before and after treatment. There is a peak at 961.42 cm⁻¹ which corresponds to the major phosphate band. The after treatment sample gave an essentially identical Raman spectrum to the before treatment sample, including the location of the phosphate band at 961.42 cm⁻¹. This implies that the added material is identical to that originally present and is a somewhat surprising result.

TABLE 2 Raman peaks positions of human tooth enamel before and after treatment Position before Position after Band treatment treatment ν₁ 961 961 PO₄ ³⁻ ν₂ 445 444 PO₄ ³⁻ ν₃ 1072 1069 PO₄ ³⁻ ν₄ 579 579 PO₄ ³⁻

The Raman bands V₁, V₂, V₃, and V₄ are characteristic of the crystallinity/perfection of the apatite crystal lattice.

Example 6 Dual Phase Gel Product

A product was prepared comprising two gel compositions: Gel I and Gel II. Details are given in Table 4. An MSC powder as described above under “step I” was incorporated into Gel I by the method disclosed under “step I”. Gel II was prepared by adding sodium alginate to a solution of phosphate buffer and sodium fluoride.

TABLE 4 dual phase gel product MCS Alginate Powders Powders Phosphate Fluoride (wt %) (wt %) (mM) (mM) Gel I 5 3 0 0 Gel II 0 3 25 25

The product was applied by mixing equal weights of Gel I and Gel II and painting the mixture (total weight 2 g) onto six teeth using a cotton bud. The treated teeth were immersed in human saliva (15 ml) for one hour, at 37° C., with gentle agitation. After this time, the teeth were rinsed and cleaned using a cotton bud to remove any remaining gel. They were then placed into fresh saliva for a further two hours. This process was performed twice a day for two weeks, giving a total of 28 treatments.

In a further experiment, Example 6 as described above (i.e. a 1:1 by weight mixture of Gel I and Gel II) was applied to an adhesive plastic tape. Then the tape was then wrapped around each tooth and the wrapped teeth immersed in saliva for eight hours. The dosage applied was 2 g of the mixture of Gel I and Gel II per 6 teeth. After this time, the teeth were rinsed with water and then put into fresh saliva. This procedure was repeated for two weeks, including a tooth brushing each day to simulate real life usage.

The effects of the above treatments with Example 6, with respect to tooth whitening, were investigated together with a “control” treatment involving tooth brushing (once a day) and treatment with saliva only.

The whitening effect was measured using a Minolta Chromameter CR-321 (3 mm aperture, 45/0) to quantitatively measure the L* and b* value of each tooth before and after treatment. L* represents the overall light intensity that is reflected from the tested surface and b* represents the light contribution from the yellow-blue. Tooth whitening is indicated by an increase in reflected light intensity (L*) and a decrease in “yellowness” (b*). The results are shown in Table 5. Average colour changes after two weeks treatment are expressed as ΔL* and Δb*. Good whitening effects were observed with both treatments according to the invention.

TABLE 5 Whitening effect following treatment with Example 6 Application ΔL* ΔL* Treatments Painting on 1.88 −1.08 Strip 4.99 −2.24 Control Saliva only 0.57 −0.91

Examples 7-9 Dual Phase Toothpaste Products

TABLE 6 Composition details First Composition Second Component 7 8 9 A Composition Calcium silicate 30 20 10 — — Fine ground natural 10 20 30 40 — chalk NaH₂PO₄ — — — — 6.4 Na₃PO₄ — — — — 7.6 Sorbitol (70% aqu.) 20 20 20 20 64 PEG 1500 — — — — 2 Abrasive silica — — — — 9 Thickening silica — — — — 4.8 Sodium lauryl sulphate 13.5 13.5 13.5 13.5 — Sodium 0.2 0.2 0.2 0.2 0.5 carboxymethylcellulose Flavour 1 1 1 1 1 Saccharine 0.3 0.3 0.3 0.3 0.3 Water and minors* 25 25 25 25 4.4 *0.25% potassium nitrate, 0.05% formaldehyde, and 0.15% triclosan in each “First Composition”.

With reference to Table 6:

Example 7 1:1 by weight mixture of First Composition 7 and the Second Composition Example 8 1:1 by weight mixture of First Composition 8 and the Second Composition Example 9 1:1 by weight mixture of First Composition 9 and the Second Composition Example A 1:1 by weight mixture of First Composition A and the Second Composition

These Examples were used to treat polished tooth enamel blocks. The treatment involved brushing with a slurry of the dual phase toothpaste in water (1 part toothpaste to 2 parts water) for 3 minutes, followed by incubation of the blocks in saliva for 2 hours at 37° C. This procedure was performed twice a day over a four week period. A conventional “whitening” toothpaste was used as a control, as was water.

The colour of the tooth enamel blocks was monitored using a Chromameter, as described above. The final results are indicated in Table 7, ΔL* and ΔW* representing the changes in “lightness” and “whiteness” between before and after treatment. “W” is a “whiteness measure” calculated as:

W=100−√{(100−L*)² +a* ² +b* ²}

TABLE 7 whitening results following use of dual phase toothpaste products Example used ΔL* ΔW* 7 2.32 1.91 A 1.21 1.09 Toothpaste 0.73 0.36 control Water control 0.56 0.21

These results indicate that Example 7 gives superior “lightening” and “whitening” in comparison with the controls.

The L* value on use of Example 7 was found to increase over time. This result is illustrated by the Figures in Table 8.

TABLE 8 Effect of duration of treatment Treatment (weeks) 0 1 2 3 4 L* 63.52 64.82 65.37 65.85 65.84

The effect of the treatments on the hardness of the polished tooth enamel blocks was also investigated. This was done by measuring Knoop hardness using a HM-122 hardness testing machine (from Mitutoyo, Japan). 10 samples were measured for each treatment and 5 indentations made for each sample. The results shown in Table 9 illustrate that Examples 8 and 9 led to a significant increase (p<0.05) in enamel hardness.

TABLE 9 hardness results following use of dual phase toothpaste products Hardness (GPa) Example used Before After 8 266 318 9 276 333 A 281 271 Toothpaste 274 287 control Water control 296 283

The effect of the treatments on the roughness of the polished tooth enamel blocks was also investigated. This was done using a surface profilometer (SV2000 from Mitutoyo, Japan). 10 samples were measured for each treatment. The results shown in Table 10 illustrate that Examples 8 and 9 led to a significant decrease in enamel roughness, i.e., a significant increase in smoothness and shine.

TABLE 10 effect of treatments on enamel roughness Roughness Example used change (%) 8 −10.9 9 −10.2 A +5.2 Toothpaste +20 control Water control −2.2

In an independent study, the effect of the treatments upon the whiteness of whole teeth was examined. The experimental procedure was essentially the same as that described with respect to the polished tooth enamel blocks (described above), the only difference being the use of whole teeth. The results indicated in Table 11 illustrate the superior efficacy of Example 7 in comparison with a conventional whitening toothpaste.

TABLE 11 whitening results on whole teeth Example used ΔL* Δb* ΔW* 7 1.76 −0.77 1.88 Toothpaste 0.20 −0.28 0.26 control

Example 10 Dual Phase Toothpaste Product

The two compositions detailed in Table 12 are intended for use in a 1:1 by weight ratio. These compositions are suitable for extrusion as independent compositions/phases from within the same compartment of the same tube, for example with the first composition forming a core and the second composition forming a surrounding sheath. The amount of water in the compositions of this Example is particularly low.

TABLE 12 dual phase toothpaste for contact extrusion First Second Component Composition Composition Calcium silicate 20 — Na₂HPO₄ — 10 Sorbitol (70% aqu.) 48 61 PEG 1500 2 2 Abrasive silica 9 9 Thickening silica 8.5 7.5 Sodium lauryl sulphate 6.6 6.6 Sodium 0.6 0.6 carboxymethylcellulose Flavour 1.3 1.3 Saccharine 0.2 0.2 Water and minors* 3.8 1.8 *2 ppm blue pigment in the “First Composition”.

Example 11 Dual Phase Toothpaste Product

The two compositions (“First” and “Second”) detailed in Table 13 are intended for use in a 1:1 by weight ratio.

TABLE 13 First Second Component Composition Composition Calcium silicate 20 — NaH₂PO₄ — 10 Sorbitol (70% aqu.) 60 60 PEG 1500 2 2 Abrasive silica 2 8 Thickening silica 8 6 Sodium lauryl sulphate 3 3 Sodium 0.4 0.8 carboxymethylcellulose Flavour 1 — Saccharine 0.1 0.1 Titanium dioxide — 5 Water 3.5 5.1 

1. An oral care product comprising a first composition comprising an insoluble calcium salt that is not a calcium phosphate salt, a second independent composition comprising a source of phosphate ions, and a means for delivering each of the compositions to the surface of the teeth.
 2. An oral care product according to claim 1, wherein the insoluble calcium salt is a calcium silicate.
 3. An oral care product according to claim 2, wherein the calcium silicate has a Ca:Si ratio of from 1:3 to 3:1.
 4. An oral care product according to claim 1, wherein the insoluble calcium salt is a bio-material.
 5. An oral care product according to claim 1, wherein the insoluble calcium salt is mesoporous.
 6. An oral care product according to claim 5, wherein the mesoporous calcium salt has an average pore size (diameter) of preferably from 0.4 to 4 nm.
 7. An oral care product according to claim 1, wherein the insoluble calcium salt is present in the first composition at from 5 to 20% by weight of said composition.
 8. An oral care product according to claim 1, wherein the first composition comprises less 0.1% by weight of phosphate ions.
 9. An oral care product according to claim 1, wherein the first composition has a pH of from 8.5 to
 10. 10. An oral care product according to claim 1, wherein the source of phosphate ions is a water-soluble salt.
 11. An oral care product according to claim 1, wherein one or more of the compositions is applied as a gel treatment.
 12. An oral care product according to claim 1, wherein the means of delivery involves a dual tube having a first compartment for the first composition and a second, independent compartment for the second composition.
 13. An oral care product according to claim 1, wherein the means of delivery involves a tape, in particular an adhesive tape, onto which one or preferably both of the compositions are applied, prior to the strip being placed in contact with the teeth.
 14. An oral care product according to claim 1, wherein the means of delivery involves a single tube having the first composition and second composition present as independent compositions within the same tube.
 15. An oral care product according to claim 14, wherein the quantity of water within each of the compositions is less than 30% by weight.
 16. An oral care product according to claim 15, wherein the first composition has less than 20% by weight of water and the second composition has less than 25% by weight of water.
 17. A method of remineralising and/or whitening the teeth comprising the steps of treating the teeth with a first composition comprising an insoluble calcium salt that is not a calcium phosphate salt and a second independent composition comprising a source of phosphate ions.
 18. A product comprising a first composition comprising an insoluble calcium salt that is not a calcium phosphate salt in combination with a second independent composition comprising a source of phosphate ions for use as a medicament.
 19. The use of a first composition comprising an insoluble calcium salt that is not a calcium phosphate salt in combination with a second independent composition comprising a source of phosphate ions for the manufacture of an oral care product.
 20. The use according to claim 19 for the whitening of teeth.
 21. The use according to claim 19 for the treatment of dental erosion.
 22. The use according to claim 19 for the treatment of tooth decay.
 23. The use according to claim 19 for the treatment of sensitive teeth. 